The present invention relates to precision liquid handlers for pharmaceutical, drug development and similar laboratory applications, and more specifically to a plate locator for holding and accurately positioning sample well plates in a liquid handler.
In pharmaceutical, genomic and proteomic research and drug development laboratories, and other biotechnology applications, automated liquid handlers are used for handling laboratory samples in a variety of laboratory procedures. For example, liquid handlers are used for biotechnological and pharmaceutical liquid assay procedures, sample preparation, compound distribution, microarray manufacturing and the like. An automated liquid handler has a work bed that supports an array of sample receptacles. One-piece sample containing plates having an integral array of many sample containing receptacles or wells are widely used. A typical liquid handler has a probe or an array of multiple probes that are moved into alignment with one or more wells to carry out liquid handling operations such as adding liquid to the wells.
It is desirable to decrease the volumes of samples treated with automated liquid handlers. Sample containing plates with a footprint of about three and one-half by five inches and having an X-Y array of 96 wells in an eight by twelve well pattern have been widely used. In order to increase throughput and to reduce consumption of sample constituents, these plates are being superceded by microplates of the same footprint but having an array of smaller wells, for example 384 wells in a sixteen by twenty-four array. This trend is continuing, and there is a need for an automated liquid handler able to accommodate microtiter plates having a very dense array of a very large number of very small volume wells for sample volumes in the nanoliter range. For example, some microtiter plates presently in use have the same footprint as previously used plates but have 1,536 wells in a thirty-two by forty-eight well array.
Microtiter plates with a dense array of small, closely spaced wells present serious problems for an automated liquid handler. In operation, the handler must be precise enough to place every probe of a multiple probe array in exact alignment with a corresponding number of sample containing wells. As well size and spacing decreases, it becomes more difficult for an automated handler to reliably place the liquid handling probes directly over selected sample containing wells.
The margin for error in locating the plates and wells on the work bed of the handler and for positioning the probes relative to the plates and wells decreases as well array density increases. One aspect of the problem is the precise and consistent location of the plates and wells upon the work bed. Approaches such as using manually adjustable clamps or workholders can accurately locate the sample containing plates upon the work surface, but this type of system requires a high degree of operator skill and care, a large number of delicate manual operations and excessive consumption of time in setting up a bed of plates for treatment in the liquid handler. In addition this type of system is not well suited for automated, robotic placement of plates on the bed. It would be desirable to provide a plate locator that is easy and quick to use, that does not require great operator skill, that accommodates robotic placement and that accurately holds and positions sample containing plates on the work bed of a liquid handler.
A principal object of the present invention is to provide an improved plate locator for positioning and holding sample containing plates on the work bed of a precision liquid handler. Other objects are to provide a plate locator that consistently achieves precise plate positioning; that is easy to use and does not require great care or skill to locate plates on the work bed; that is suited to robotic placement of plates on the work bed; and that is simple and inexpensive yet reliable and rugged.
In brief, in accordance with the invention there is provided a plate locator for positioning and holding a four sided plate having an array of sample containing wells, such as a microplate, on a work bed of a precision liquid handler having at least one probe for registration with at least one well of the plate. The plate locator apparatus includes a flat, planar locator bed adapted to be secured to the work bed of the precision liquid handler. A plate receiving nest on the locator bed has four sides corresponding to the four sides of the four sided plate. The nest includes rigid stop members extending up from the bed on first and second sides of the nest and movably mounted holders extending up from the bed at third and fourth sides of the nest opposite the rigid stop members at the first and second sides of the nest Resilient biasing elements are connected between the bed and each of the movably mounted holders for urging the holders toward the center of the nest.